Chromatin template activity during aging in WI38 cells

Influence of Growth State on Relationship between Nuclear Template Activity and in vitro ‘Ageing’

“…However, they are in contrast to those of Ryan (1975) and Ryan and Cristofalo (1975) who observed a decline in the template activity of chromatin isolated from early (45% life span completed) and late (65% life span completed) passage logarithmically growing WI-38 cells. However, a number of authors have expressed reservations concerning the use of isolated chro matin to study template activity (Butterworth et ai, 1971 ;Tsai and Saunders, 1973;Maryanka and Gould, 1973;Ryan and Cristofalo, 1975), and apparent discrepancies may be due to the different methodologies or methods of chromatin preparation used (see 'Discussion' in Whatley and Hill, 1980). Studies of free RNA polymerase activity suggested that this was correlated with the level of bound polymerase activity until the end of the life span when there was a decrease in the ratio of free to bound enzyme.…”

“…Ageing processes which act on the genome could be expressed as altered or faulty nuclear transcription, and studies of chromatin function have been reported by vari ous authors {Macieira- Coelho et al, 1966;Ryan and Cristofalo, 1975;Ryan, 1975;Bowman et al, 1976;Hill et al, 1978). Their results are, however, often seemingly conflict ing, and this makes it difficult to draw overall conclusions about the relationship between nuclear transcription and in vitro 'ageing'.…”

“…Isolated nuclei have been used, since this overcomes the problems associated with cellular permeability barriers to RNA precur sors, while allowing the nuclear chromatin to retain properties which are close to the in vivo state. This system is therefore more suitable than the use of isolated chromatin preparations, which has been criticised by other authors (Butterworth et al, 1971;Keshgegian and Furth, 1972;Tsai and Saunders, 1973;Ryan and Cristofalo, 1975). We have analysed both total nuclear template activity and RNA II polymerase activity, and results indicate that these measurements seemed to reflect the in vivo rate of RNA synthesis during physiological transitions.…”

“…Several authors have attempted to relate cellular changes with altered molecular events {Cristofalo, 1972;Macieira-Coelho et al, 1975;Ryan and Cristofalo, 1975), but no clear molec ular mechanism has yet been established for in vitro 'ageing'. Ageing processes which act on the genome could be expressed as altered or faulty nuclear transcription, and studies of chromatin function have been reported by vari ous authors {Macieira- Coelho et al, 1966;Ryan and Cristofalo, 1975;Ryan, 1975;Bowman et al, 1976;Hill et al, 1978).…”

Changes in Chromatin Structure along Aging

“…In fact, according to [27], cell senescence is characterized by a reduction of cell metabolism and a restriction on DNA transcription and proliferative capacity, being all of this associated with increased condensed chromatin. The reduction of template activity of chromatin was also found in aged normal female embryonic lung WI38 cells [28]. Contrarily, as it was observed in submandibular glands from rats [29], cultured aged skin fibroblasts [30], and mouse hepatocytes [31], chromatin unpackages with aging with a consequent increase in the template activity.…”